The present invention relates to the field of intravascular radiation therapy. In particular, the present invention relates to an intravascular radiation therapy to inhibit restenosis of a vessel.
Coronary artery balloon angioplasty is a minimally invasive technique developed as an alternative to coronary artery bypass grafting for treatment of atherosclerosis, the principle process of heart disease. There are about 450,000 coronary interventions, i.e., angioplasty, atherectomy, and stent procedures, performed annually in the U.S. However, a major limitation of this clinical procedure is the high prevalence of restenosis, or re-narrowing, of the treated vessel. Restenosis occurs approximately 30-50% of the time.
Restenosis occurs as a result of injury to the vessel wall due to the angioplasty procedure, or other procedures, such as stenting, and/or atherectomy. Restenosis is a complex process, which can involve an immediate vascular recoil, neointimal hyperplasia, and/or late vascular remodeling. Neointimal hyperplasia, a response of the body to balloon-induced physical injury of the vessel wall, is thought to be the main contributor to restenosis. Hyperplasia can result in narrowing of the vessel lumen within 3-6 months after angioplasty due to proliferation of smooth muscle cells in the region injured by the angioplasty. Restenosis can require the patient to undergo repeat angioplasty procedures or by-pass surgery with added costs and risks to the patient.
One procedure currently used to inhibit restenosis involves delivery of a prescribed dose of radiation to the injured portion of the vessel using intravascular radiation therapy (IRT). IRT procedures typically utilize radioimagery systems, such as fluoroscopy, to position a radiation source within the injured length of the vessel, for example, the dilated portion of the vessel. The radioimagery system allows a radiation source, as well as radio-opaque markers, to be viewed in vivo.
For example, once a procedure, such as an angioplasty, is completed, the physician may freeze-frame the radio-image on a viewer, such as a fluoroscope, so that anatomical landmarks may be used to subsequently position a radiation source within the dilated area. Typically, a catheter is inserted into the vessel and positioned within the dilated portion of the vessel. Catheters used in IRT commonly have an elongate, tubular shaft for receiving a radiation source that will deliver the prescribed radiation therapy. Some catheters have markers, for example, radio-opaque markers, which denote the area of the catheter in which the radioactive source will be located. The markers may be viewed using the radioimagery system to assist in positioning the catheter within vessel.
Once the catheter is positioned, a radiation source is then advanced through the lumen of the catheter shaft, and positioned within the dilated portion of the vessel. Some IRT procedures utilize a radiation source, such as radioactive seeds sealed within a source lumen, in which the source is visible on the radioimagery system, i.e., the fluoroscope. Other systems utilize radioactive sources that are not easily viewed, and, therefore, utilize markers, such as radio-opaque markers, that are visible on the radioimagery system. These markers can be used to mark one or both ends of the radiation source.
FIG. 1 illustrates a longitudinal cross-sectional view of one example of a method in the prior art for inhibiting restenosis using IRT. Following dilation of a vessel 10 using an angioplasty balloon length of 22 mm, the angioplasty balloon is removed and a catheter 12 is inserted and positioned within the dilated length. In this example, the catheter 12 may be a centering catheter designed to substantially center a radiation source 16 within the vessel 10. The catheter 12 has radio-opaque proximal and distal markers 14A and 14B that are designed to be visible using radioimagery. The markers 14A and 14B demarcate the area within which the radiation source is located to allow positioning of the catheter 12 within the vessel. The catheter 12 may be positioned using standard radioimagery techniques well known in the art in which, for example, a fluoroscope is used to observe the incremental movement of the catheter 12 until the dilated length of the vessel 10 is approximately centered between the proximal and distal markers 14A and 14B. In this example, the proximal and distal markers 14A and 14B delineate a 27 mm region to provide a 5 mm margin of error in positioning the dilated length (22 mm) within the radio-opaque markers 14A and 14B. A 27 mm radioactive source 16, such as a radioactive source wire, is then inserted and positioned within the catheter 12 so that the source end marker 18 is positioned over the distal radio-opaque marker 14B on the catheter 12. In this way the radioactive source 16 is located between the markers 14A and 14B. The radioactive source 16 is left in place until a prescribed radiation dose has been delivered to the vessel, and is then withdrawn.
A problem in current intravascular radiotherapy systems is the occurrence of an edge effect, or severe narrowing, at one or more ends of the irradiated region. A possible cause of edge effects is delivering a therapeutic dose of radiation that is too short in length to prevent restenosis throughout the treated vessel. Several factors may be responsible for not treating an adequate length of the injured vessel. Some of these have been defined as positioning errors, underestimating the length of the injury which may be longer than the dilation length due to the possibility of traumatizing segments of the vessel adjacent to the injury, and radiation dose fall-off.
Positioning of the radiation source relative to the freeze-framed image is difficult due to some movement of the vessel resulting from patient movement, blood flow, heart beats, and breathing. Thus, the radiation source may not be correctly positioned within the injured portion of the vessel, resulting in a geographical miss.
A further contributor to geographical misses, results from the projected angle of view by the radioimagery system. With radioimagery systems, such as fluoroscopy, the projected view is foreshortened so that distances appear shorter than a true perpendicular view would provide. Thus, positioning of a radiation source using a radio-image may result in the source being incorrectly positioned relative to the vessel injury.
In some cases, a minimum radiation source length may be chosen to treat a vessel injury in an attempt to prevent overdosing of non-injured lengths of vessel. If the radiation source was initially incorrectly positioned as earlier described, the selection of a minimum radiation source may result in some portions of the injured vessel left untreated.
Sometimes, during the intravascular procedures previous to the IRT, additional procedures are undertaken that cause more injury to a vessel than was anticipated. For example, if a stent does not fully deploy, the balloon used to deploy the stent may be inflated to a higher pressure, or may be moved around in an attempt to fully deploy the stent. The higher inflation pressure and movement may cause damage to the vessel in areas adjacent to the main dilated or stented length. In another example, a small blockage may be dilated outside a larger blockage in an attempt to touch-up the vessel and open it up. If this is done in several locations, often the radiation source is not positioned to treat the touched up areas. In a third example, during a balloon dilation or stenting procedure, the balloon shoulders may stretch or tear the vessel in areas adjacent to the main dilated or stented area resulting in a longer portion of the vessel being injured. When a radiation source is inserted to deliver a prescribed dose of radiation to the procedurally expected injured portions of the vessel, these additionally damaged areas may not be known and may not receive a prescribed dose of radiation.
Even if a radiation source is correctly positioned within the injured portion of a vessel, a prescribed dose of radiation may not be delivered along the entire length of the source. Some radiation sources have a dose fall-off region at the ends of the source where a lower dose of radiation is delivered than in the middle of the source. These fall-off regions vary with the particular radiation source.
FIG. 2 illustrates an example of a longitudinal dose profile of a radiation source within a centering catheter in the prior art. In one example, a therapeutic dose of radiation may be defined as at least an isodose line at 80% of a prescribed dose at 1 mm in tissue, for example, 80% of 20 Gy at 1 mm in tissue; and, a sub-therapeutic dose may be defined as a dose below an isodose line at 80% of a prescribed dose at 1 mm in tissue. It is to be understood that a therapeutic dose of radiation may be differently defined depending upon the radiation source and treatment therapy.
The dose distribution illustrates that if a 27 mm radiation source 16 is positioned correctly within the proximal and distal markers 14A and 14B, the 27 mm radiation source 16 delivers a full therapeutic dose of radiation along a length of about 22 mm with a 2-2.5 mm dose fall off at each end of the radiation source. Thus, the 27 mm radiation source 16 delivers a full therapeutic dose of radiation along a length that is shorter than the total length of the radiation source. This leaves little to no margin for treating injured lengths beyond the dilated length and does not allow room for positioning errors arising from the treatment system or physician.
Additionally, animal studies indicate that a 32P radiation dose in the range of 5-11 Gy at 1 mm into the vessel can produce a negative, proliferative response in the vessel. This dose range may be termed a proliferative dose, and may result in restenosis, or renarrowing of the vessel, in the portions of the vessel that received the proliferative dose. As a result, vessels with maximum dilated lengths may have portions of injured tissue adjacent to each side of the dilated length which may receive a less than therapeutic dose of radiation, and may actually receive a proliferative dose of radiation, inducing edge effects.
As illustrated in the examples above, it is difficult to determine where a therapeutic dose of radiation is being delivered to an injured length of vessel. Further, it is difficult to determine if additional damage exists in the vessel, and if that additional damage is receiving a therapeutic dose of radiation, or perhaps a proliferative dose of radiation.
Thus, a need exists for a method and/or apparatus that delivers a therapeutic dose of radiation over an adequate length of a vessel to prevent restenosis following intravascular procedures such as angioplasty or stenting. Further, the method and/or apparatus should enable visualization of the length within which the therapeutic dose is delivered.
The present invention includes methods and apparatuses for positioning a radiation source in vivo relative to radio-opaque markers on a catheter that delineate a therapeutic treatment length so that a therapeutic dose of radiation is delivered along the therapeutic treatment length.